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MPM Non-invasive Imaging Of Biological Interactions Following Drug Delivery With Micro-nanoprojection Patches.
Funder
National Health and Medical Research Council
Funding Amount
$403,612.00
Summary
The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery devi ....The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery device is a set of microscopic nanoneedles coated with drug substance and applied to the skin as a small patch. The device is practical, needle-free and pain-free. The aim of this current project is to use the micro-nanoprojection array patches-configured to uniquely deliver biomolecules to cells within given strata-to find: 1) what delivery sites of antigen-expression plasmid- toll like receptor (TLR) agonist lead to strong humoral immune responses in the intact animal. 2) whether delivery of different TLR agonists have different effects on the maturation and migration of the different professional antigen presenting cells (APCs) in the skin, as visualised locally by Multi-Photon Microscopy (MPM). 3) whether differences in APC maturation and migration are associated with different systemic antibody responses. We will identify optimal delivery sites of drugs-vaccines to the skin (layer, cells targeted, duration of delivery) with MPM for desired systemic immune responses. This will have important contributions towards improving immunotherapeutics of major diseases via skin targeting with micro-nanoprojection array patch technologies (and other methods).Read moreRead less
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
CD4+CD8β+ Double-positive T-cell Regulation Of CD8 T-cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$430,983.00
Summary
T-cells are a type of white blood cell that play an essential role in the immune system. CD4+CD8+ Double-Positive (DP) T-cells are a rare and poorly defined T-cell subset associated with skin disease - however their function and subsequently their contribution to disease is not known. Our preliminary data suggest that these DP cells may regulate the function of other immune populations in the skin. This project aims to deliver key insights into DP cells and their role in skin disease.
Investigation Of Cellular Abnormalities And Synapse Formation In DOCK8 Immunodeficiency
Funder
National Health and Medical Research Council
Funding Amount
$318,284.00
Summary
Why do some people get allergies? Or serious infections? To investigate this we will study mice and humans with a mutation in the DOCK8 gene. People with mutations in the DOCK8 gene get Hyper-IgE Syndrome and develop severe viral infections of the skin as well as allergic disease. By investigating how DOCK8 works in the cells of the immune system, we hope to understand why these infections and allergies occur and find out why these problems can also happen in those without this specific genetic ....Why do some people get allergies? Or serious infections? To investigate this we will study mice and humans with a mutation in the DOCK8 gene. People with mutations in the DOCK8 gene get Hyper-IgE Syndrome and develop severe viral infections of the skin as well as allergic disease. By investigating how DOCK8 works in the cells of the immune system, we hope to understand why these infections and allergies occur and find out why these problems can also happen in those without this specific genetic defect.Read moreRead less
Dendritic Cell-mediated Induction Of T Cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Australia has some of the highest rates of immune-mediated diseases in the world. These diseases include autoimmune, allergic and inflammatory conditions. We will use a mouse model to study how dendritic cells can prevent the onset of these conditions by inactivating the immune cells that cause them. Our findings will aid in understanding why these diseases develop and how they may be prevented and treated.
Antigen Recognition By CD1a-restricted T Cells In The Human Immune System
Funder
National Health and Medical Research Council
Funding Amount
$615,520.00
Summary
Human immunity requires protective T cells that target foreign molecules for removal. Even though substantial populations of T cells exist that recognise lipid molecules, little is known about their basic biology. We will identify and characterise lipid reactive human T cells and examine their response to foreign or self-lipids expressed by infectious organisms and host cells. This work will have important implications in understanding lipid reactive T cells in health and disease.
We have identified a population of immune cells called ‘resident memory T cells’ that reside in tissues of the body. These resident memory T cells play an important role in controlling infections, but it is also apparent that they can lead to aberrant immune reactions, causing autoimmune diseases. This project aims to further our understanding of these immune cells, including how they can be identified and generated, and how they can be controlled to prevent disease.
Subset Determination Of Tissue-Resident T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$473,394.00
Summary
Immunity relies on white blood cells called T cells that circulate around the body and which are also found permanently lodged at body surfaces. It is non-circulating T cells that are the most important in protecting against infection. In this application we propose to show that only a subset of T cells can form the resident population and to identify the molecules that determine T cell residency. This information can then be used for the efficient construction of disease preventing vaccines.
The body’s surfaces are continually under threat from microbes that may cause debilitating disease. Our ability to control such infections relies on our immune system, consisting of different cell types with specialised functions. We will study frontline immune cells that populate barrier tissues such as skin and mucosa where they provide enhanced local protection by responding vigorously on infection. Our studies will guide the development of future therapies harnessing our immune system.
Regulation Of Tissue-Resident Memory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$494,554.00
Summary
A recently identified subset of T cells that reside in the skin are critical to combat viral infection. However, little is known about how these T cell populations are formed. This project will characterise the pathways required to generate these cells and will identify novel factors that regulate their development. A greater understanding of how these T cells can be generated will open the way to utilise these cells in new vaccine strategies.